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Preconditioning the human heart
1Harefield Hospital, Middlesex.
Insights
Ischaemic preconditioning, involving short bursts of reduced blood flow, may protect the human heart during coronary artery bypass grafting (CABG) surgery. This method showed reduced myocardial injury by preserving adenosine triphosphate (ATP) and lowering troponin T release.
Area of Science:
- Cardiology
- Cardiac Surgery
- Ischemia-Reperfusion Biology
Background:
- Ischaemic preconditioning is a known phenomenon that protects the myocardium from injury in animal models.
- The potential for inducing ischaemic preconditioning in the human heart during cardiac surgery remained to be investigated.
Purpose of the Study:
- To determine if ischaemic preconditioning can be safely induced in human patients undergoing coronary artery bypass grafting (CABG).
- To assess the efficacy of ischaemic preconditioning in limiting myocardial injury during CABG surgery.
Main Methods:
- Two randomized studies were conducted during CABG.
- Study 1 measured myocardial adenosine triphosphate (ATP) levels from biopsies at different time points.
- Study 2 measured serum troponin T release post-cardiopulmonary bypass (CPB).
- Preconditioning involved two 3-minute cross-clamping periods with 2 minutes of reperfusion, followed by 10 minutes of sustained ischemia; control group received only sustained ischemia.
Main Results:
- Preconditioned hearts showed a significantly slower rate of ATP depletion during sustained ischemia (11.5 vs 7.2 mumol/g dry weight; P < 0.005).
- Troponin T release was significantly lower at 72 hours post-CPB in the preconditioned group (0.3 vs 1.4 milligrams; P < 0.05).
- More patients in the preconditioned group had troponin T levels below 0.5 milligram at 72 hours (10 vs 3).
Conclusions:
- Ischaemic preconditioning can be induced in human patients undergoing CABG.
- The findings suggest that ischaemic preconditioning reduces myocardial injury during CABG, evidenced by improved myocardial ATP levels and decreased troponin T release.
Abstract:
The phenomenon of ischaemic preconditioning protects the myocardium by limiting infarct size in animal models of ischaemia and reperfusion. Ischaemic preconditioning may be induced by short periods of ischaemia and reperfusion. We investigated whether the human heart can be ischaemically preconditioned during coronary artery bypass grafting (CABG). Patients were enrolled into two separate studies. In the first study myocardial adenosine triphosphate (ATP) was used as the measured endpoint, assayed from myocardial biopsies taken at onset of cardiopulmonary bypass (CPB), at the end of the preconditioning stimulus, and at the end of a 10 min sustained ischaemic insult. In the second study the release of myocardial troponin T was used as the endpoint; taken at pre-CPB, and at 1, 6, 24, and 72 h after CPB. In both studies, patients were randomised into either the preconditioning group or the control group. Preconditioning was induced, after the onset of CPB, with two 3 min periods of crossclamping and an intervening 2 min of reperfusion, followed by 10 min sustained ischaemia. The control group only received 10 min of sustained ischaemia. Ischaemic preconditioning resulted in a slower rate of ATP (mumol/g dry weight) depletion in the preconditioned hearts at the end of the 10 min of sustained ischaemia (preconditioned: 11.5 +/- 0.8 vs control: 7.2 +/- 0.3; P < 0.005). Also, preconditioning resulted in a slower rate of troponin T release which was significantly different at 72 h after CPB in the preconditioned group (0.3 milligram) when compared with the control group (1.4 milligrams; P < 0.05). In addition, more patients in the preconditioned group had troponin T levels lower than 0.5 milligram at 72 h than in the control group (10 vs 3 patients). Both groups of patients received the same number of grafts, and underwent the same length of ischaemia during the procedure. We conclude that in patients undergoing CABG surgery, ischaemic preconditioning may reduce myocardial injury as shown by the favourable changes in myocardial ATP, and serum troponin T levels.